Cyclin-dependent kinase 5 (Cdk5) is a neuronal kinase that has been implicated in many diverse processes in the central nervous system. Cdk5 has been shown to regulate dopamine signaling in the neostriatum and is a molecular target of chronic cocaine exposure. We intend to investigate the role Cdk5 plays in glutamtatergic neurotransmission in the ventral striatum (nucleus accumbens). Of particular interest is the role of Cdk5 in dopamine signaling, the main target of drugs of abuse. Using Cre/loxP technology, a conditional cdk5 knockout mouse has been generated to allow temporal control of tissue-specific knockout of Cdk5. The effect of striatal loss of Cdk5 on dopamine signaling pathway will be assessed using a pharmacological approach combined with quantitative immunoblotting. The electrpphysiological properties of striatal neurons will be defined following loss of Cdk5. These studies will be conducted following chronic cocaine exposure, in order to better define the role of Cdk5 in the neostriatum.